KCNC3_HUMAN
ID KCNC3_HUMAN Reviewed; 757 AA.
AC Q14003;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Potassium voltage-gated channel subfamily C member 3;
DE AltName: Full=KSHIIID;
DE AltName: Full=Voltage-gated potassium channel subunit Kv3.3;
GN Name=KCNC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-63, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Lens epithelium;
RX PubMed=10712820; DOI=10.1006/exer.1999.0796;
RA Rae J.L., Shepard A.R.;
RT "Kv3.3 potassium channels in lens epithelium and corneal endothelium.";
RL Exp. Eye Res. 70:339-348(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 291-651.
RA Lee J.E., Garbutt J.H., Phillips K.L., Roses A.D.;
RT "A human chromosome 19 Shaw type potassium channel gene.";
RL Submitted (JAN-1992) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HAX1 AND ACTR3, AND
RP DOMAIN.
RX PubMed=26997484; DOI=10.1016/j.cell.2016.02.009;
RA Zhang Y., Zhang X.F., Fleming M.R., Amiri A., El-Hassar L., Surguchev A.A.,
RA Hyland C., Jenkins D.P., Desai R., Brown M.R., Gazula V.R., Waters M.F.,
RA Large C.H., Horvath T.L., Navaratnam D., Vaccarino F.M., Forscher P.,
RA Kaczmarek L.K.;
RT "Kv3.3 channels bind Hax-1 and Arp2/3 to assemble a stable local actin
RT network that regulates channel gating.";
RL Cell 165:434-448(2016).
RN [5]
RP CHARACTERIZATION OF VARIANTS SCA13 HIS-420; HIS-423 AND LEU-448, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=22289912; DOI=10.1113/jphysiol.2012.228205;
RA Minassian N.A., Lin M.C., Papazian D.M.;
RT "Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type
RT 13.";
RL J. Physiol. (Lond.) 590:1599-1614(2012).
RN [6]
RP CHARACTERIZATION OF VARIANTS SCA13 HIS-366; HIS-420; HIS-423 AND LEU-448,
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH KCNC1, AND
RP MUTAGENESIS OF ARG-366; ARG-420 AND ARG-423.
RX PubMed=23734863; DOI=10.1042/bj20130034;
RA Zhao J., Zhu J., Thornhill W.B.;
RT "Spinocerebellar ataxia-13 Kv3.3 potassium channels: arginine-to-histidine
RT mutations affect both functional and protein expression on the cell
RT surface.";
RL Biochem. J. 454:259-265(2013).
RN [7]
RP CHARACTERIZATION OF VARIANTS SCA13 HIS-420 AND LEU-448, SUBCELLULAR
RP LOCATION, AND GLYCOSYLATION.
RX PubMed=25152487; DOI=10.1016/j.nbd.2014.08.020;
RA Gallego-Iradi C., Bickford J.S., Khare S., Hall A., Nick J.A.,
RA Salmasinia D., Wawrowsky K., Bannykh S., Huynh D.P., Rincon-Limas D.E.,
RA Pulst S.M., Nick H.S., Fernandez-Funez P., Waters M.F.;
RT "KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia
RT 13 displays aberrant intracellular trafficking.";
RL Neurobiol. Dis. 71:270-279(2014).
RN [8]
RP VARIANTS SCA13 HIS-420 AND LEU-448, CHARACTERIZATION OF VARIANTS SCA13
RP HIS-420 AND LEU-448, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16501573; DOI=10.1038/ng1758;
RA Waters M.F., Minassian N.A., Stevanin G., Figueroa K.P., Bannister J.P.A.,
RA Nolte D., Mock A.F., Evidente V.G.H., Fee D.B., Mueller U., Duerr A.,
RA Brice A., Papazian D.M., Pulst S.M.;
RT "Mutations in voltage-gated potassium channel KCNC3 cause degenerative and
RT developmental nervous system phenotypes.";
RL Nat. Genet. 38:447-451(2006).
RN [9]
RP VARIANTS SCA13 HIS-366; HIS-420 AND HIS-423, CHARACTERIZATION OF VARIANTS
RP SCA13 HIS-366 AND HIS-423, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19953606; DOI=10.1002/humu.21165;
RA Figueroa K.P., Minassian N.A., Stevanin G., Waters M., Garibyan V.,
RA Forlani S., Strzelczyk A., Buerk K., Brice A., Duerr A., Papazian D.M.,
RA Pulst S.M.;
RT "KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial
RT ataxia patients.";
RL Hum. Mutat. 31:191-196(2010).
RN [10]
RP VARIANT SCA13 HIS-423, VARIANT ASP-263, CHARACTERIZATION OF VARIANT
RP ASP-263, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21479265; DOI=10.1371/journal.pone.0017811;
RA Figueroa K.P., Waters M.F., Garibyan V., Bird T.D., Gomez C.M., Ranum L.P.,
RA Minassian N.A., Papazian D.M., Pulst S.M.;
RT "Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13
RT (SCA13).";
RL PLoS ONE 6:E17811-E17811(2011).
RN [11]
RP VARIANTS SCA13 ASN-129; HIS-420; HIS-423; ASN-477; MET-535; GLY-591;
RP SER-643; ARG-645 AND ASN-746, VARIANTS HIS-41 AND GLY-63, CHARACTERIZATION
RP OF VARIANTS SCA13 ASN-129; HIS-420; HIS-423; ASN-477; MET-535; GLY-591;
RP SER-643; ARG-645 AND ASN-746, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25756792; DOI=10.1371/journal.pone.0116599;
RA Duarri A., Nibbeling E.A., Fokkens M.R., Meijer M., Boerrigter M.,
RA Verschuuren-Bemelmans C.C., Kremer B.P., van de Warrenburg B.P.,
RA Dooijes D., Boddeke E., Sinke R.J., Verbeek D.S.;
RT "Functional analysis helps to define KCNC3 mutational spectrum in dutch
RT ataxia cases.";
RL PLoS ONE 10:E0116599-E0116599(2015).
CC -!- FUNCTION: Voltage-gated potassium channel that plays an important role
CC in the rapid repolarization of fast-firing brain neurons. The channel
CC opens in response to the voltage difference across the membrane,
CC forming a potassium-selective channel through which potassium ions pass
CC in accordance with their electrochemical gradient. The channel displays
CC rapid activation and inactivation kinetics (PubMed:10712820,
CC PubMed:26997484, PubMed:22289912, PubMed:23734863, PubMed:16501573,
CC PubMed:19953606, PubMed:21479265, PubMed:25756792). It plays a role in
CC the regulation of the frequency, shape and duration of action
CC potentials in Purkinje cells. Required for normal survival of
CC cerebellar neurons, probably via its role in regulating the duration
CC and frequency of action potentials that in turn regulate the activity
CC of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (By
CC similarity). Required for normal motor function (PubMed:23734863,
CC PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:25756792).
CC Plays a role in the reorganization of the cortical actin cytoskeleton
CC and the formation of actin veil structures in neuronal growth cones via
CC its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).
CC {ECO:0000250|UniProtKB:Q63959, ECO:0000269|PubMed:10712820,
CC ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606,
CC ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912,
CC ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25756792,
CC ECO:0000269|PubMed:26997484}.
CC -!- SUBUNIT: Homotetramer. Heterotetramer with KCNC1 (PubMed:23734863).
CC Interacts (via C-terminus) with HAX1 (PubMed:26997484). Identified in a
CC complex with ACTR3, a subunit of the Arp2/3 complex; this interaction
CC is indirect and depends on the presence of HAX1 (PubMed:26997484).
CC Interaction with HAX1 modulates channel gating (PubMed:26997484).
CC {ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:26997484}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10712820,
CC ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606,
CC ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912,
CC ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487,
CC ECO:0000269|PubMed:25756792, ECO:0000269|PubMed:26997484}; Multi-pass
CC membrane protein {ECO:0000255}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q63959}; Multi-pass membrane protein
CC {ECO:0000255}. Perikaryon {ECO:0000250|UniProtKB:Q63959}. Cell
CC projection, axon {ECO:0000250|UniProtKB:Q63959}. Cell projection,
CC dendrite {ECO:0000250|UniProtKB:Q63959}. Cell projection, dendritic
CC spine membrane {ECO:0000250|UniProtKB:Q01956}; Multi-pass membrane
CC protein {ECO:0000255}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:26997484}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:26997484}. Note=Detected on Purkinje cell dendritic
CC spines, positioned perisynaptically but also in extrasynaptic positions
CC along the spine membranes (By similarity). Detected at presynaptic
CC calices of Held (By similarity). Colocalizes with the cortical actin
CC cytoskeleton and the Arp2/3 complex (PubMed:26997484).
CC {ECO:0000250|UniProtKB:Q01956, ECO:0000250|UniProtKB:Q63959,
CC ECO:0000269|PubMed:26997484}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. {ECO:0000305}.
CC -!- DOMAIN: The cytoplasmic N-terminus mediates N-type inactivation.
CC {ECO:0000269|PubMed:26997484}.
CC -!- DOMAIN: The C-terminal cytoplasmic tail contributes to the regulation
CC of channel inactivation and to the interaction with HAX1 and the Arp2/3
CC complex. {ECO:0000269|PubMed:26997484}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:25152487}.
CC -!- DISEASE: Spinocerebellar ataxia 13 (SCA13) [MIM:605259]:
CC Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar
CC ataxia (ADCA) characterized by slow progression and variable age at
CC onset, ranging from childhood to late adulthood. Intellectual
CC disability can be present in some patients.
CC {ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606,
CC ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912,
CC ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487,
CC ECO:0000269|PubMed:25756792}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the potassium channel family. C (Shaw) (TC
CC 1.A.1.2) subfamily. Kv3.3/KCNC3 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF055989; AAC24118.1; -; mRNA.
DR EMBL; AC008655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z11585; CAA77671.1; -; Genomic_DNA.
DR CCDS; CCDS12793.1; -.
DR PIR; S19552; S19552.
DR RefSeq; NP_004968.2; NM_004977.2.
DR RefSeq; XP_006723266.1; XM_006723203.2.
DR RefSeq; XP_011525228.1; XM_011526926.1.
DR AlphaFoldDB; Q14003; -.
DR SMR; Q14003; -.
DR BioGRID; 109950; 33.
DR IntAct; Q14003; 1.
DR STRING; 9606.ENSP00000434241; -.
DR ChEMBL; CHEMBL2362996; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q14003; -.
DR TCDB; 1.A.1.2.13; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q14003; 3 sites.
DR iPTMnet; Q14003; -.
DR PhosphoSitePlus; Q14003; -.
DR BioMuta; KCNC3; -.
DR DMDM; 212276500; -.
DR jPOST; Q14003; -.
DR MassIVE; Q14003; -.
DR MaxQB; Q14003; -.
DR PaxDb; Q14003; -.
DR PeptideAtlas; Q14003; -.
DR PRIDE; Q14003; -.
DR ProteomicsDB; 59785; -.
DR ABCD; Q14003; 1 sequenced antibody.
DR Antibodypedia; 18827; 305 antibodies from 30 providers.
DR DNASU; 3748; -.
DR Ensembl; ENST00000477616.2; ENSP00000434241.1; ENSG00000131398.15.
DR GeneID; 3748; -.
DR KEGG; hsa:3748; -.
DR MANE-Select; ENST00000477616.2; ENSP00000434241.1; NM_004977.3; NP_004968.2.
DR UCSC; uc002pru.1; human.
DR CTD; 3748; -.
DR DisGeNET; 3748; -.
DR GeneCards; KCNC3; -.
DR GeneReviews; KCNC3; -.
DR HGNC; HGNC:6235; KCNC3.
DR HPA; ENSG00000131398; Tissue enhanced (brain, thyroid gland).
DR MalaCards; KCNC3; -.
DR MIM; 176264; gene.
DR MIM; 605259; phenotype.
DR neXtProt; NX_Q14003; -.
DR OpenTargets; ENSG00000131398; -.
DR Orphanet; 98768; Spinocerebellar ataxia type 13.
DR PharmGKB; PA30027; -.
DR VEuPathDB; HostDB:ENSG00000131398; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000163131; -.
DR InParanoid; Q14003; -.
DR OMA; WMIERTS; -.
DR OrthoDB; 818306at2759; -.
DR PhylomeDB; Q14003; -.
DR TreeFam; TF352511; -.
DR PathwayCommons; Q14003; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q14003; -.
DR SIGNOR; Q14003; -.
DR BioGRID-ORCS; 3748; 126 hits in 1082 CRISPR screens.
DR ChiTaRS; KCNC3; human.
DR GeneWiki; KCNC3; -.
DR GenomeRNAi; 3748; -.
DR Pharos; Q14003; Tclin.
DR PRO; PR:Q14003; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q14003; protein.
DR Bgee; ENSG00000131398; Expressed in kidney epithelium and 146 other tissues.
DR ExpressionAtlas; Q14003; baseline and differential.
DR Genevisible; Q14003; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central.
DR GO; GO:0032591; C:dendritic spine membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003974; K_chnl_volt-dep_Kv3.
DR InterPro; IPR005404; K_chnl_volt-dep_Kv3.3.
DR InterPro; IPR021105; K_chnl_volt-dep_Kv3_ID.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF11404; Potassium_chann; 1.
DR PRINTS; PR01582; KV33CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01498; SHAWCHANNEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Disease variant;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Methylation;
KW Neurodegeneration; Phosphoprotein; Postsynaptic cell membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome;
KW Spinocerebellar ataxia; Synapse; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..757
FT /note="Potassium voltage-gated channel subfamily C member
FT 3"
FT /id="PRO_0000054055"
FT TOPO_DOM 1..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 291..309
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..370
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 371..379
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..398
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..434
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..469
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TRANSMEM 518..539
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..757
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..78
FT /note="Important for normal N-type inactivation"
FT /evidence="ECO:0000269|PubMed:26997484"
FT REGION 210..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 503..508
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..63
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..604
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 625
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q63959"
FT MOD_RES 686
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63959"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63959"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 41
FT /note="Q -> H (in dbSNP:rs185017345)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074192"
FT VARIANT 63
FT /note="D -> G (in dbSNP:rs375912738)"
FT /evidence="ECO:0000269|PubMed:10712820,
FT ECO:0000269|PubMed:25756792"
FT /id="VAR_074193"
FT VARIANT 129
FT /note="D -> N (in SCA13; unknown pathological significance;
FT changes channel activity; shifts the voltage dependence of
FT activation)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074194"
FT VARIANT 263
FT /note="G -> D (variant of uncertain significance; changes
FT channel activity; activates more quickly and deactivates
FT more slowly)"
FT /evidence="ECO:0000269|PubMed:21479265"
FT /id="VAR_074195"
FT VARIANT 366
FT /note="R -> H (in SCA13; unknown pathological significance;
FT dominant negative that decreases channel activity;
FT decreases protein abundance; decreases protein stability;
FT decreases localization to the plasma membrane; no effect on
FT tetramerization; dbSNP:rs769502387)"
FT /evidence="ECO:0000269|PubMed:19953606,
FT ECO:0000269|PubMed:23734863"
FT /id="VAR_074196"
FT VARIANT 420
FT /note="R -> H (in SCA13; dominant negative that induces
FT loss of channel activity; decreases protein abundance;
FT decreases protein stability; decreases localization to the
FT plasma membrane and alters the localization of the wild-
FT type protein; impairs N-glycosylation; no effect on
FT tetramerization; dbSNP:rs104894699)"
FT /evidence="ECO:0000269|PubMed:16501573,
FT ECO:0000269|PubMed:19953606, ECO:0000269|PubMed:22289912,
FT ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487,
FT ECO:0000269|PubMed:25756792"
FT /id="VAR_029530"
FT VARIANT 423
FT /note="R -> H (in SCA13; dominant negative that reduces
FT channel activity; alters gating; decreases protein
FT abundance; decreases localization to the plasma membrane;
FT no effect on tetramerization; dbSNP:rs797044872)"
FT /evidence="ECO:0000269|PubMed:19953606,
FT ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912,
FT ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25756792"
FT /id="VAR_074197"
FT VARIANT 448
FT /note="F -> L (in SCA13; alters gating; slows channel
FT closing; decreases protein abundance; no effect on
FT localization to the plasma membrane; no effect on N-
FT glycosylation; no effect on tetramerization;
FT dbSNP:rs104894700)"
FT /evidence="ECO:0000269|PubMed:16501573,
FT ECO:0000269|PubMed:22289912, ECO:0000269|PubMed:23734863,
FT ECO:0000269|PubMed:25152487"
FT /id="VAR_029531"
FT VARIANT 477
FT /note="D -> N (in SCA13; unknown pathological significance;
FT no effect on channel activity; dbSNP:rs148033381)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074198"
FT VARIANT 535
FT /note="V -> M (in SCA13; changes channel activity; shifts
FT the voltage dependence of activation)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074199"
FT VARIANT 591
FT /note="S -> G (in SCA13; unknown pathological significance;
FT reduces channel activity; shifts the voltage dependence of
FT activation; dbSNP:rs549394447)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074200"
FT VARIANT 643
FT /note="G -> S (in SCA13; unknown pathological significance;
FT no effect on channel activity; dbSNP:rs778523009)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074201"
FT VARIANT 645
FT /note="P -> R (in SCA13; unknown pathological significance;
FT no effect on channel activity; dbSNP:rs1460306526)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074202"
FT VARIANT 746
FT /note="D -> N (in SCA13; unknown pathological significance;
FT no effect on channel activity; dbSNP:rs958323371)"
FT /evidence="ECO:0000269|PubMed:25756792"
FT /id="VAR_074203"
FT MUTAGEN 1..78
FT /note="Missing: Loss of N-type inactivation."
FT /evidence="ECO:0000269|PubMed:26997484"
FT MUTAGEN 366
FT /note="R->K,A: Decreases protein abundance."
FT /evidence="ECO:0000269|PubMed:23734863"
FT MUTAGEN 420
FT /note="R->K,A: Decreases protein abundance."
FT /evidence="ECO:0000269|PubMed:23734863"
FT MUTAGEN 423
FT /note="R->K,A: Decreases protein abundance."
FT /evidence="ECO:0000269|PubMed:23734863"
FT MUTAGEN 592
FT /note="G->R: Loss of interaction with ACTR3. No effect on
FT voltage-dependent channel opening or current amplitude, but
FT decreased rate of inactivation during prolonged
FT depolarization."
FT /evidence="ECO:0000269|PubMed:26997484"
SQ SEQUENCE 757 AA; 80578 MW; B44306B850DFD797 CRC64;
MLSSVCVSSF RGRQGASKQQ PAPPPQPPES PPPPPLPPQQ QQPAQPGPAA SPAGPPAPRG
PGDRRAEPCP GLPAAAMGRH GGGGGDSGKI VINVGGVRHE TYRSTLRTLP GTRLAGLTEP
EAAARFDYDP GADEFFFDRH PGVFAYVLNY YRTGKLHCPA DVCGPLFEEE LGFWGIDETD
VEACCWMTYR QHRDAEEALD SFEAPDPAGA ANAANAAGAH DGGLDDEAGA GGGGLDGAGG
ELKRLCFQDA GGGAGGPPGG AGGAGGTWWR RWQPRVWALF EDPYSSRAAR YVAFASLFFI
LISITTFCLE THEGFIHISN KTVTQASPIP GAPPENITNV EVETEPFLTY VEGVCVVWFT
FEFLMRITFC PDKVEFLKSS LNIIDCVAIL PFYLEVGLSG LSSKAAKDVL GFLRVVRFVR
ILRIFKLTRH FVGLRVLGHT LRASTNEFLL LIIFLALGVL IFATMIYYAE RIGADPDDIL
GSNHTYFKNI PIGFWWAVVT MTTLGYGDMY PKTWSGMLVG ALCALAGVLT IAMPVPVIVN
NFGMYYSLAM AKQKLPKKKN KHIPRPPQPG SPNYCKPDPP PPPPPHPHHG SGGISPPPPI
TPPSMGVTVA GAYPAGPHTH PGLLRGGAGG LGIMGLPPLP APGEPCPLAQ EEVIEINRAD
PRPNGDPAAA ALAHEDCPAI DQPAMSPEDK SPITPGSRGR YSRDRACFLL TDYAPSPDGS
IRKATGAPPL PPQDWRKPGP PSFLPDLNAN AAAWISP
